A principal-stress rule for cell division in epithelia

Abstract

Dense active materials, from cellular tissues to jammed and glassy systems, must continuously relieve internal mechanical stress to remain structurally stable as they are driven far from equilibrium. In epithelial tissues, this relief occurs through cell division, yet what sets the geometry of this structural remodeling event has, for over a century, been attributed to a purely geometric principle: Hertwig’s rule, whereby cells divide along their long axis. We show that as epithelial tissues densify and cell shape anisotropy collapses, this geometric rule is superseded by a mechanical one in which dense epithelia relieve anisotropic stress by cells dividing along their principal axis, independent of the tissue’s isotropic stress state. Using direct force measurement and stress inference, we show that stress orientation, rather than cell shape, governs the axis of cell division across mechanically distinct systems, from fluid-like to jammed monolayers and structurally heterogeneous organoids, remaining predictive precisely where the classical geometric rule fails. This stress-oriented remodeling is reciprocally coupled to the material’s mechanical state: anisotropic stress accelerates the underlying remodeling rate, while each remodeling event locally dissipates the stress that triggered it, closing a negative feedback loop. This “principal-stress rule” recasts epithelial cell division as a stress-relief mechanism intrinsic to dense active matter, providing a general mechanical framework linking internal stress, structural remodeling, and homeostasis in living materials.

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Cite

BibTeX RIS

BibTeX

@article{anger2026principalstress,
  title = {{A principal-stress rule for cell division in epithelia}},
  author = {Lucas Anger and Tianxiang Ma and Fanny Wodrascka and Andreas Schoenit and Kristian Thijssen and Satish Kailasam Mani and Marc-Antoine Fardin and Carine Rosse and René-Marc Mège and Amin Doostmohammadi and Benoit Ladoux},
  journal = {Nature Communications},
  year = {2026},
  month = sep,
  doi = {10.1038/s41467-026-77813-5},
  url = {https://hal.science/hal-05797449v1},
  note = {CC BY-NC-ND 4.0},
}

RIS

TY  - JOUR
TI  - A principal-stress rule for cell division in epithelia
AU  - Lucas Anger
AU  - Tianxiang Ma
AU  - Fanny Wodrascka
AU  - Andreas Schoenit
AU  - Kristian Thijssen
AU  - Satish Kailasam Mani
AU  - Marc-Antoine Fardin
AU  - Carine Rosse
AU  - René-Marc Mège
AU  - Amin Doostmohammadi
AU  - Benoit Ladoux
PY  - 2026
DA  - 2026/09/23
JO  - Nature Communications
DO  - 10.1038/s41467-026-77813-5
UR  - https://hal.science/hal-05797449v1
AB  - Dense active materials, from cellular tissues to jammed and glassy systems, must continuously relieve internal mechanical stress to remain structurally stable as they are driven far from equilibrium. In epithelial tissues, this relief occurs through cell division, yet what sets the geometry of this structural remodeling event has, for over a century, been attributed to a purely geometric principle: Hertwig’s rule, whereby cells divide along their long axis. We show that as epithelial tissues densify and cell shape anisotropy collapses, this geometric rule is superseded by a mechanical one in which dense epithelia relieve anisotropic stress by cells dividing along their principal axis, independent of the tissue’s isotropic stress state. Using direct force measurement and stress inference, we show that stress orientation, rather than cell shape, governs the axis of cell division across mechanically distinct systems, from fluid-like to jammed monolayers and structurally heterogeneous organoids, remaining predictive precisely where the classical geometric rule fails. This stress-oriented remodeling is reciprocally coupled to the material’s mechanical state: anisotropic stress accelerates the underlying remodeling rate, while each remodeling event locally dissipates the stress that triggered it, closing a negative feedback loop. This “principal-stress rule” recasts epithelial cell division as a stress-relief mechanism intrinsic to dense active matter, providing a general mechanical framework linking internal stress, structural remodeling, and homeostasis in living materials.
SN  - 2041-1723
SN  - 2041-1723
ER  -

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